Device and method for diluting a sample

ABSTRACT

The present invention provides a pump device  50  which is usable to dilute a sample  52  before analysis. A first pump  54  pumps the sample to a mixing region  58  where it mixes with a diluent  66 . A second pump  64  pumps the diluted sample to the analysis instrument. The flow of the diluent to the mixer is equal to the difference of the flow of the sample to the mixer and the flow of the diluted sample to the instrument. Pumps  54  and  64  are independently controllable by a controller unit which is arranged so that data from the instrument can be used to determine the dilution factor of the sample. Thus, the controller can control this dilution factor in real time, upon receipt of such data from the instrument, by change either one of (or both) the pump&#39;s flow rate.

PRIOR APPLICATIONS

This application is a divisional application of U.S. patent applicationSer. No. 10/524,382 filed Sep. 30, 2005, now U.S. Pat. No. 7,998,434issued Aug. 16, 2011, which claims the benefit of Patent CooperationTreaty Application Number PCT/GB2003/003569, filed Aug. 14, 2003, whichclaims priority from Great Britain Application Number 0218946.2, filedAug. 14, 2002, all of which are incorporated herein by reference. Thisinvention relates to U.S. patent application Ser. No. 10/524,706 with anInternational Filing Date of Aug. 14, 2003, entitled, “Method AndApparatus for Pumping And Diluting A Sample” assigned to a commonassignee.

FIELD OF THE INVENTION

This invention relates to a method and apparatus for diluting a samplebefore performing mass spectrometry on the sample.

The invention is described herein with reference to liquid samples whichrequire dilution before they are analysed in a mass spectrometer.However, the invention is not limited to liquid samples and can equallyapply to dissolved or suspended samples.

DESCRIPTION OF THE RELATED ART

Analysis equipment for analysing trace elements in liquids have alimited capability of measuring samples which contain relatively highlevels of dissolved solid material, or matrix (such as CaCO₃ ordissolved salts in water, or the like). The trace elements of interestto the user are often only a few parts per billion, or lower, whilst thematrix can be many parts per million, or higher. Such high levels ofmatrix can have undesirable effects on the analytical equipment, such asdeposition of materials on orifices, glassware, or ion optical elements,unless the sample is appropriately diluted.

Inductively coupled plasma mass spectrometers (ICP-MS) typically requirea total dissolved solid level of less than 2000 mg/l to avoid thisso-called swamping effect. The dissolved solids which are deposited oncomponents within the instrument, for example on the cones which samplethe plasma and skim off a portion of the supersonic jet, significantlyreduces the reliability of a test result and the results of any othersubsequent test. If deposition of materials occurs, the instrument hasto be thoroughly cleaned before accurate testing can resume.

Test laboratories are often required to analyse many samples quicklywhere the matrix content of each sample varies widely. Typically, theuser would wish to dilute each sample by a certain amount to determinethe analytes present in each sample, and whether the sample can beanalysed undiluted. If dilution is required, this initial test providesan indication of the dilution factor necessary to bring the totaldissolved solids down to a level tolerated by the instrument.

Such manual intervention is too cumbersome, time consuming and costly ifmany samples per day require analysis. Presently, samples whichintroduce too great a loading of dissolved solids for the instrument tocope with are re-analysed once the analyser has been cleaned. Analysismust cease for instrument cleaning, and samples inadvertently analysedafter contamination has occurred must be re-analysed. These additionalsteps require considerable operator intervention. Such a limit to thethroughput of samples is undesirable and operator intervention iscostly.

Automated dilution systems have been used previously and, referring toFIG. 1, such an automated system 10 known in the art is shown in highlyschematic form. A sample 12 is drawn from a container by a sample pump14 to a mixing tube 16. Similarly, a diluent 18 is drawn by a diluentpump 20 to the mixing tube 16 from a separate diluent container. Thesample is diluted in the mixing tube where it is completely mixed withdiluent. An instrument pump 22 draws the diluted sample from the mixingtube and into the instrument or analyser, not shown in FIG. 1.

Both the sample and diluent pumps have to be able to maintain accuratelyflow rates to ensure the sample is diluted precisely. If the dilution isnot maintained to a known level and within a relatively tight tolerance,the accuracy of the analysis results may be unacceptable. Likewise, theinstrument flow must be maintained at an accurate flow rate to ensurethe diluted sample is pumped to the analyser's input at a known,controllable rate. Thus, all the pumps (and their associated flow rates)need to be controlled accurately to maintain accurate test results.

Presently, peristaltic pumps are used to pump the sample, diluent anddiluted sample through the dilution system. Typically, dilutions ratiosof 50:1 of diluent to sample are used for mass spectroscopy. Hence, thediluent pump rate is typically fifty times greater than the sample pumprate. Peristaltic pumps have a limited range of flow rates and thesample and diluent pumps often operate at the extremes of their flowrate range. Also, the limited flow rate for peristaltic pumps limits thedilution factor by which the sample can be diluted.

The rate at which the diluted sample enters the instrument (not shown)depends on the type of instrument being used but is relatively low andtypically a few millilitres per minute. Typically, the combined flowrates of the sample and diluent pumps exceeds the instrument pump flowrate. This is because all the pumps have a relatively similar range offlow rates in which they can operate. Thus, for example, at dilutionfactors greater than ten, the dilution pump 20 must be operating at ahigh flow rate which typically exceeds the acceptable flow rate of theanalysis instrument. It is, therefore, necessary to provide a wasteoutlet 24 to prevent build up of pressure in the system; excess dilutedsample not pumped to the instrument flows to a waste container 26. Athigh dilution factors, the solution flowing to waste can exceed thesolution entering the analyser by as much as a factor of fifty.Materials in the waste container are discarded and, since high qualitydiluent necessary for accurate test results is relatively expensive,this wastage is an additional economic burden on test laboratories.

Other types of pumps, such as syringe pumps can also used. Syringe pumpsrequire the syringe to draw up the fluid (be it the sample or diluent)before it is pumped to the analysis instrument. A series of valves istherefore required to ensure the correct flow of fluid through thesystem. The additional time required to draw the fluid into the syringelimits the laboratory's (or analysis instrument's) ability to test manysamples over a period of time. Furthermore, the time required to controlthe valves further limits the throughput of test samples, and extracontrol algorithms may be necessary for the system controller to controlthe valves, further increasing system complexity.

A pumping system similar to the ones described above is disclosed inU.S. Pat. No. 5,007,297 (Pacific Scientific Company).

Another automated pumping system 28 known in the art is shown in FIG. 2in highly schematic form. Sample 29 is pumped along a first pipe 30 by asyringe pump 31 to fill the syringe (not shown). A valve 32 is closed toprevent fluid entering the syringe from the pump discharge pipe 33. Whenthe pump is charged with an appropriate amount of sample, the valve isopened and the syringe plunger driven at a constant rate to provide aflow of sample along pipe 33 in the general direction indicated by arrowZ. A one way valve in the pump (not shown) prevents the sample fromflowing back to the container 29 during the phase sample flow along pipe33.

A mixing region 34 of the pipe is defined by a second pipe 35 adjoiningpipe 33 in a generally “T” or “Y” shaped configuration. As solution isaspirated by the instrument pump system (for example, a nebuliser), anuncontrolled pressure drop is produced in pipe 35. This causes anuncontrolled flow of solution along pipe 33′ from the mixing region 34.This flow rate is a combination of a controlled flow of solution fromthe syringe pump, and an uncontrolled flow of diluent along pipe 35. Theinability to control the flow of diluent results in an uncontrolleddilution factor. There is no instrument pump to pump the diluted sampleto the analyser in this arrangement.

Problems arise with systems which rely on this arrangement. Forinstance, there are limits to the dilution factor this system canprovide, especially if the analyser requires the diluted sample to bepumped at a specific rate. This problem could be overcome by providingan instrument pump and pressure relief system, similar to that shown inFIG. 1. However, the problems associated with the system in FIG. 1 nowbecome prevalent with this system, for example, diluent wastage.

U.S. Pat. No. 4,804,519 describes a sample analysis apparatus. A motordrives a pair of pumps with the same angular velocity, but differentpump rates are achieved by using tubes with different internal diameterin each pump. This arrangement requires the tube of one or both of thepumps to be removed from the system whenever a different flow rate ofsolution through a pump is required.

U.S. Pat. No. 4,245,509 describes a sampling apparatus which usessyringe pumps to pump fluids through a mixing region. Each syringe isarranged so that each of the syringe's plungers are moved at the samerate. Thus, a difference in flow rates of fluid flowing from eachsyringe is only controlled by changing syringe diameter and/or tubediameter.

US 2002/0011437 A1 describes a liquid chromatograph system whichcontrols a mixing ratio of two liquids by independently controlling theflow rate of two pumping devices, each of which pumps a differentliquid, before the liquids reach a mixing region.

SUMMARY OF THE INVENTION

It is an aim of the present invention to ameliorate the problemsassociated with the prior art. Furthermore, it is an aim of the presentinvention to provide an apparatus which improves upon known systems inmass spectrometry. More specifically, there is provided a massspectrometer pumping device for supplying a diluted sample to a massspectrometric analyser, comprising: a mixer arranged to mix a samplewith a diluent to form the diluted sample, said mixer being disposedbetween a first and a second conduit such that, in use, a sample entersthe mixer through the first conduit at a first flow rate and a diluententers the mixer through the second conduit at a second flow rate, themixer being arranged so that said diluted sample exits the mixer througha third conduit at a third flow rate, said third flow rate beingsubstantially equal to the sum of the first and second flow rates; pumpmeans for pumping fluid through the mixer and into the analyser; and apump controller arranged to receive data from the analyser indicative ofthe amount by which the sample is diluted and to control the pump meansso that any of the first, second or third flow rates are adjustable withrespect to one another in dependence upon the received data.

There is yet still provided a method for diluting a sample prior toperforming mass spectrometry on the sample in an analyser, using a pumpsystem comprising a first pump means, a diluent for diluting the sample,a mixer for mixing the sample and diluent, a first conduit disposedbetween a sample container and the mixer, a second conduit disposedbetween a diluent container and the mixer, and a third conduit disposedbetween the mixer and the analyser, wherein the pump means draws samplethrough the mixer, so that the flow rate of diluted sample along thethird conduit is substantially the sum of the flow rate of diluent alongthe second conduit and the flow rate of sample along the first conduit,and a controller controls the pumps means to adjust the first, second orthird flow rates with respect to one another in dependence upon datareceived from the analyser indicative of the amount by which the sampleis diluted.

The embodiments have an advantage of reducing system complexity,increasing dilution factor range over which the system can operateacceptably, increasing sample throughput, and decreasing operatorintervention. Providing a feedback of data from the analyser to the pumpcontroller can provide near instantaneous automatic control of theamount by which the sample is diluted. This reduces the need foroperator intervention, for instance, and can greatly improve the timeefficiency of the analyser.

Embodiments of the present invention have a further advantage of areduced number of pumps required to dilute the sample accurately beforeit is analysed with a substantial improvement to the range of dilutionfactors. The pump system and the dilution factor can be more easilycontrolled to better accuracy levels. The time taken to change samplesfor dilution is greatly reduced using embodiments of the presentinvention, thus increasing the number samples which might be tested byan analyser. Also, virtually no diluent is wasted during normaloperation.

A further aspect of the present invention resides in the method furtherincluding: i) replacing the sample container with the another samplecontainer containing a second sample: ii) varying the first rate tosubstantially the third rate for a predetermined time; and iii) afterthe predetermined time, reducing to first rate so that the sample isdiluted by a dilution factor; wherein the predetermined time issubstantially the time taken for the second sample to be transferredfrom the another container to the mixer at the first rate.

This further aspect has the advantage of substantially reducing the timetaken to exchange samples for dilution and hence increases the number ofsamples which can be tested or analysed over a given time period.

The present invention provides an additional method for diluting asample prior to performing mass spectrometry on the sample in ananalyser, using a pump system comprising, a first pump means, a secondpump means, a diluent for diluting the sample, a mixer for mixing thesample and diluent, a first pipe disposed between a sample container andthe mixer, a second pipe disposed between a diluent container and themixer, and a third pipe disposed between the mixer and the analyser, thefirst pump means being arranged to pump the sample or the diluent at afirst or second flow rate along the first or second pipe respectively,to the mixer, the second pump means being arranged to pump the diluentor diluted sample at a second or third flow rate along the second orthird pipe to the mixer or analyser respectively: the method comprising;a) pumping the diluted sample between the mixer and the analyser at thethird rate; b) pumping the sample at an initial rate for a predeterminedtime; c) after the predetermined time, reducing the initial rate to thefirst rate; d) mixing the sample with a diluent to dilute the sample;and e) controlling the first or second pump means to adjust the first,second or third flow rates in dependence upon data received from theanalyser indicative of the amount by which the sample is diluted,wherein, the initial rate is substantially the third rate, thepredetermined time is the time taken for the sample to be transferredfrom the container to the mixer at the initial rate, and the third,second or first flow rate respectively is substantially equal to thedifference between the second and first, third and first, or third andsecond flow rates respectively.

The present invention provides a yet further method supplying a dilutedsample to a mass spectrometric analyser for analysis, comprising;diluting a sample by mixing said sample with a diluent in a mixer,pumping said diluted sample to the analyser from the mixer, andcontrolling the dilution factor by which the sample is diluted bycontrolling the flow rate of the sample and/or diluent to the mixer,wherein the controlling of the dilution factor step is carried out inresponse to data received by a pump controller from the analyser.

Embodiments of the invention have further advantages of substantiallyreducing the operator intervention, and increase the sample throughputrate. The embodiments aim to provide automated dilution of the sample ata consistent and safe level before the sample is introduced into theanalyser. Dilution of the sample to a safe level also has the advantageof allowing the required precision of analysis to be carried out ontrace levels within the sample by automatic dilution of the sample. Thesample throughput can also be increased by a relatively rapidintroduction of new (or different) sample solutions up to the mixingregion by controlling the flow rate of the sample uptake. The cost ofdiluting samples can be reduced by reducing the amount of diluent usedby the dilution system; only the volume of diluent required to dilutethe sample to a required safe level can be consumed and little or nodiluent is wasted. (By ‘safe level’, we mean a dilution factor necessaryto avoid contamination of the analysis instrumentation.)

DESCRIPTION OF THE DRAWINGS

Embodiments of the present invention will now be described, by way ofexample, with reference to the accompanying drawings, in which:

FIG. 1 is a schematic diagram of a pump system known in the art anddescribed above;

FIG. 2 is a schematic diagram of a pump system known in the art anddescribed above;

FIG. 3 is a schematic diagram of another pump system embodying thepresent invention;

FIG. 4 is a schematic diagram of a pump system that is an alternativeembodiment of the pump system shown in FIG. 3;

FIG. 5 is a schematic diagram of a pump system that is anotheralternative embodiment of the pump system shown in FIG. 3; and

FIG. 6 is a schematic diagram of a pump system that is yet anotheralternative embodiment of the pump system shown in FIG. 3.

DETAILED DESCRIPTION OF AN EMBODIMENT

Referring to FIG. 3, a pump system 50 embodying the present invention isshown in schematic form. A sample 52 to be analysed is drawn from acontainer by a first pump 54 along a first pipe 56 to a mixing section58. The end of the first pipe at which the sample enters the system iscompletely submersed in the sample to ensure no air enters the system.At the mixing section, the first pipe 56 is joined to a second pipe 60to form a single pipe 62.

The mixer is a “Y” or “T” configured junction in the tubing or pipes.Other, more complex arrangements of pipe joints might be used whichensure thorough mixing of the fluids entering the mixing region from thefirst and second pipes. The exit of the mixing section comprises asingle pipe 62 disposed between the mixing section and a second pump 64which pumps fluid from the mixing section to an instrument (not shown)for analysis.

Mixing of the sample and diluent to form a diluted sample takes place atthe interface of the first, second and third pipes. Additional mixingmight also occur for some length along the third pipe from the mixer tothe analyser. Mixing occurs as a function of the turbulent flow of thesample and diluent at the junction and possibly along the third pipe,and also by diffusion of the two fluids. In this embodiment, mixing mayalso occur as the fluid passes through the second pump on the thirdpipe, particularly if the second pump is a peristaltic pump.

The first pump is preferably a piston type pump, similar to the milliGATpump head supplied by Global FIA Inc. (described in U.S. Pat. No.6,079,313). This type of pump allows a much greater range of flow rates,compared to peristaltic pumps for instance, and can operate tocontinuously pump relatively large or small volumes of sample at aconstant, or varying flow rate, as desired. Furthermore, this type ofpump can operate at very low flow rates (typically in the region ofmicro litres per minute) with the accuracy and precision required forICPMS applications. This piston pump system does not suffer thedisadvantages associated with the prior art systems describedpreviously. The second pump may be the same type as the first pump, or,if appropriate, may be a (much cheaper) peristaltic pump. Of course, thefirst and second pumps are operable at different flow rates with respectto one another, and independently of each other.

A diluent 66 is drawn from a diluent container 67, up the second pipe 60to the mixing section 58 where it mixes with the sample, and hencedilutes the sample. The end of the second pipe at which the diluententers the system is completely submersed in the diluent to ensure airdoes not enter the system. The flow from the mixer to the instrument ofthe diluted sample is accurately controlled by the second pump 64 atFlow 3; the second pump is also controlled by the controller 55. Thus,when Flow 1<Flow 3, the diluent is drawn along the second pipe 60 to themixer at a flow rate Flow 2, following the equationFlow 1+Flow 2=Flow 3;assuming the liquids in the pipes are non-compressible. (The flow can bemeasured in litres per minute).

Preferably, Flow 3 is kept constant by the second pump 64, hence therate of arrival of diluted sample of the instrument is constant. Varyingthe flow rate of the first pump therefore changes the dilution factor Dby which the sample is diluted, whereD=Flow 2/Flow 1, orD=(Flow 3/Flow 1)−1.

So, from the equations above and assuming Flow 3 is constant, a decreasein the first pump's flow rate (Flow 1) increases the diluent flow to themixer section, and hence the dilution factor D.

An example of how the pump system embodying the invention can operatewith an ICP-MS instrument is now provided. During operation, all samplesare routinely diluted by a discrete predetermined dilution factor D₁before the sample is analysed. D₁ is initially set to a relatively highlevel so that the sample is diluted to such an extent that any dissolvedsolids (or matrix) in the sample are sufficiently diluted when thesample is analysed. In this way, adverse effects to the analysisinstrumentation or the test result can be prevented or reduced.Typically, D₁=100.

Analysis software which checks the analyser results determines theextent of diluted matrix in the sample, to see whether further dilutionis necessary. Also, the analysis data, or results are processed todetermine the precision of the measured analyte signal. This data can befed to the controller 55 for real time adjustment of the dilutionfactor, depending on the analysis results. For instance, if the analytesignal is too weak, the dilution factor may need to be reduced.Moreover, the instrument may not be able to measure analyteconcentration with the required accuracy if the analyte signal is toointense (in which case the sample may require further dilution by afactor D₂). Flow rate information or data can be passed from the pumps(or any flow meters—not shown) back to the controller for use by thecontroller.

Therefore, it is possible for the controller to change the dilutionfactor (if necessary) having regard for the analyser results. Forexample, if the results show too much matrix remains in the dilutedsample for accurate analysis, the controller can reduce the first pump'sflow rate, thereby increasing the dilution factor, as describedpreviously.

D₂ can be calculated by comparing the matrix signal from the analyserwith a pre-determined maximum level used for providing adequatelyaccurate results. As previously described, the new dilution factor D₂ isachieved by adjusting Flow 1 of the first pump 54. As a result, thedilution factor can be controlled in real time as analysis results aremade available from the analyser. Thus the throughput of the instrumentcan be greatly improved and less intervention from a human operator isrequired. Furthermore, if the dilution factor is maintained at arelatively high level, the inlet of the analyser can be prevented frombecoming contaminated with matrix materials, thus reducing the downtimenecessary for cleaning the instrument.

When a new, or different, sample is required for analysis the first pump54 pumps the new sample from a container at a rate just less than, orsubstantially equal to, Flow 3 for a period of T1. The period T1 iscalculated so that the new sample completely fills the first pipe fromthe mixer 58 to the first pump 54, using the equationT1=V/(Flow 1)where V is the volume of the tubing 56 from the sample uptake to themixer, including any volume occupied by the sample within the first pump54.

After time period T1 has elapsed the flow rate of the first pump isreduced, thus initiating dilution of the sample by a dilution factor, aspreviously described. The time taken for the diluted new sample to reachthe analysis instrumentation can be calculated, knowing the volume ofpipe from the mixer to the analysis instrument, including any volumeoccupied by the diluted sample in the second pump 64. Hence, theinstrument can be programmed to start the analysis of the new sampleonly when the pump system has ‘purged’ itself of any previous sampleswhich may have remained in the pumps or tubing.

In an alternative embodiment, the second pump is disposed between thediluent container and the mixing region. In this embodiment, the pumpcontroller is capable of finely balancing the flow rate of each pump sothat the flow of fluid to the analysis instrument remains constant.During the sample change over, or purge procedure described above, theinstrument (or diluent) pump can be stopped until the new sample hasbeen pumped to the junction in the mixer, at which point the diluentpump rate can be rapidly ramped up so that the new sample is diluted andpumped to the analyser for analysis. At the same time, the first flowrate is reduced so as to keep the flow to analyser constant.

A further embodiment includes an arrangement where the first pump isdisposed on the second pipe with the second pump being between the mixerand the analyser.

Another embodiment is provided by an arrangement where a single pump isdisposed between the mixer and analyser and one, or both of the flowrates in the first or second pipe is controlled by at least one valve,or variable constriction. The valve, or valves, can be controlled by thepump controller, or a separate valve controller in communication withthe pump controller. In this regard, FIG. 4 is a schematic diagram of apump system that is an alternative embodiment of the pump system shownin FIG. 3. The pump system of FIG. 4 differs from the pump system ofFIG. 3 in that, as discussed above, the pump 54 has been omitted infavor of a single pump 64, and a valve or variable constriction 101 isprovided in the first pipe 56 to control the flow rate therethrough.FIG. 5 is a schematic diagram of a pump system that is anotheralternative embodiment of the pump system shown in FIG. 3. The pumpsystem of FIG. 5 differs from the pump system of FIG. 3 in that, asdiscussed above, the pump 54 has been omitted in favor of a single pump64, and a valve or variable constriction 102 is provided in the secondpipe 60 to control the flow rate therethrough. FIG. 6 is a schematicdiagram of a pump system that is yet another alternative embodiment ofthe pump system shown in FIG. 3. The pump system of FIG. 6 differs fromthe pump system of FIG. 3 in that, as discussed above, the pump 54 hasbeen omitted in favor of a single pump 64, a valve or variableconstriction 101 is provided in the first pipe 56 to control the flowrate therethrough, and a valve or variable constriction 102 is providedin the second pipe 60 to control the flow rate therethrough.

The pump systems described above are in a ‘closed’ configuration, bywhich we mean the sample and diluent are contained in the system fromthe input to the output; there is no waste pipe (as provided by theprior art). By keeping the system closed the equations above aremaintained during operation. It is therefore important to make sure thediluent and the sample do not run out during operation to prevent airentering the system.

The tubing or pipe components of the pump system 50 should be made ofsuitably rigid materials to prevent expansion or contraction under anypressure. Such expansion or contraction is undesirable since it effectsthe volume V occupied by the sample, diluent and diluted sample. Theexpansion and contraction can be tolerated if their extent isdeterminable or predictable.

The mixer should preferably be designed to ensure full mixing of thesample and diluent by creating a turbulent flow in the mixing region ofthe pipe.

The first and second pumps should provide a substantially continuousflow, without any pulsing. The flow rate from each pump can bedetermined by using independent flow meters disposed fore or aft of therespective pump, with an appropriate feedback loop to the pumpcontroller. Alternatively, the dilution factor can be measured using aninternal standard. An appropriate software programme can be used by thecontroller to automate the dilution of the samples and change-over fromone sample to the next, as described above. The controller mightcomprise a desktop PC with appropriate input and output devices tomonitor and control the pumps, using an appropriate software programme.

An alternative method of determining the dilution factor can include“spiking” or “lacing” the sample solution with a known substance at aknown concentration level. The spike is often referred to as an InternalStandard. Analysis of the analyser's results shows how much the samplehas been diluted by the reduction of the level of known substance in theresults. Of course, the known substances should be one which is notpresent in the sample or diluent before the spike is added. Such knownsubstances might include Rhodium or Indium, for example.

To obtain very accurate dilution factor levels it is preferable to spikeboth the sample and the diluent. For example, the sample can be spikedwith 100 parts per billion (ppb) concentration levels of Rhodium and 10ppb of Indium. The diluent is not spiked with Rhodium, but is spikedwith indium at a concentration level of 10 ppb. If the sample is dilutedby, say, a factor of fifty, the Rhodium concentration is 2 ppb (afterdilution). The Indium internal standard is still at a concentrationlevel of 10 ppb as both the sample and diluent contain 10 ppb of indium.

However, the value of Rhodium concentration varies if there is aninstability in the dilution (such instability might be caused by an airbubble in the mixer, or by inconsistent mixing of sample with thediluent, for example). In the case of an air bubble passing through thesystem, the Rhodium concentration levels might read 1.2 ppb, followed by1.99 ppb on the next batch and 2.0 ppb on the last batch. This leads toa mean value of 1.73 ppb, or a 13.5% error of the expected dilutionfactor of 50:1. A correction for each batch can be made by scaling thevalues for each batch; the scaling factor for the first batch would be2/1.2, the scaling factor for the second batch would be 2/1.99 and thescaling factor for the third batch would be 2/2.0. This can eliminateany errors in perceived concentration levels of the sample, which wouldotherwise be in error had the anomaly in the dilution factor not beennoticed. This spiking, or use of an internal standard, allows fordilutions in excess of 50:1 without the risk of micro-bubbles or mixingeffects causing errors in data.

Furthermore, spiking the diluent and sample with Indium having the samelevels of concentration is advantageous, particularly in a situationwhere the sample is pumped to the mixer and fluid in the mixer is pumpedto the instrument, but diluent is not actively pumped to the mixer(i.e., there is no pump on the line between the diluent vessel and themixer, so the flow of diluent is related to the relative flows of thesample pump and instrument pump). Problems can arise when a zerodilution factor is required. To achieve zero dilution, both theinstrument and sample pumps should run with the same flow rates.However, if the sample pump is running slightly faster than instrumentpump, then a portion of the sample is forced into the diluent,contaminating the diluent. It is therefore preferable to run the samplepump with a flow rate of the order of 10% less than the instrumentpump's flow rate. This way the sample is only slightly diluted.Detecting the concentration levels of Rhodium can account for, ordetermine this small dilution factor.

The indium spike can also be used to detect and/or determine anyvariations which might occur in the sample ionisation process. In thecase of ICP-MS the ionisation occurs in a plasma torch, and variationsin the torch's consistency or plasma condition can be detected by thelevels of indium detected in the mass spectrum. This is so becauseindium concentration levels should always be 10 ppb, but if less thanthis concentration is detected then a correction can be made to factorinto the result inconsistencies in ion formation, for instance.

Embodiments of the present invention can be used with an automatedsample dispenser, or the like.

Examples of samples used by embodiments of the present invention includedrinking water, waste water, sea water, dilute acids, urine, blood,spinal fluid, dissolved solid or gaseous samples, or the like. Theseexamples are by no means exclusive, and any liquid sample which requiresanalysis can be diluted prior to entering the analyser by a system whichembodies the present invention. Of course, an appropriate diluent isrequired for different samples and the choice of diluent for a givensample does not form part of the present invention. The diluent may bede-ionised water, ethanol or the like, but whatever is most suitabledepending on the sample being analysed.

Further embodiments of the present invention will be envisaged by theskilled person. For example, the embodiments have been described usingin-line pumps, but it may be desirable to use other pumping systems.

What is claimed:
 1. A method of diluting a sample for performing traceelement spectrometry analysis of the sample, the sample comprising oneor more trace elements and matrix, the method comprising the steps of:a) diluting a portion of the sample by a dilution factor; b) analyzingthe diluted portion of the sample to determine a matrix level in thediluted portion of the sample; and c) adjusting the dilution factor tobe used when diluting the remainder of the sample based on a comparisonbetween the determined matrix level and a pre-determined matrix level.2. The method of claim 1, wherein the adjusting step is based on acomparison between the determined matrix level and a pre-determinedmaximum matrix level.
 3. The method of claim 2, wherein the adjustingstep comprises increasing the dilution factor if the determined matrixlevel is above the pre-determined maximum matrix level.
 4. The method ofclaim 2, wherein the pre-determined maximum matrix level is 2000 mg/I.5. The method of claim 2, wherein the adjusting step comprisesdecreasing the dilution factor if the determined matrix level is belowthe pre-determined maximum matrix level.
 6. The method of claim 1,wherein the diluting step comprises diluting the sample by a firstdilution factor and the adjusting step comprises adjusting the firstdilution factor to a second dilution factor based on the determinedmatrix level.
 7. The method of claim 6, wherein the first dilutionfactor is
 100. 8. The method of claim 6, wherein the second dilutionfactor is calculated by comparing the determined matrix level with apre-determined maximum matrix level.
 9. The method of claim 1, whereinthe adjusting step comprises adjusting a flow rate of a diluent relativeto a flow rate of the sample upstream of a mixing region for providingthe diluted sample.
 10. The method of claim 1, wherein the analyzingstep comprises mass analyzing the diluted sample with a massspectrometer.
 11. The method of claim 10, wherein the mass spectrometercomprises an inductively coupled plasma mass spectrometer.
 12. Themethod of claim 1, wherein the dilution factor is controlled in realtime as the matrix level is determined by the analyzing step.
 13. Amethod of diluting a sample for spectrometry analysis comprising: a)taking a portion of the sample comprising one or more trace elements andmatrix; b) diluting a portion of the sample; c) measuring aconcentration of the matrix in the diluted sample; d) controlling thedilution of the remainder of the sample based on a comparison betweenthe matrix concentration signal measured from the previously dilutedportion of the sample and a pre-determined matrix concentration level.14. A sample dilution device in combination with an analyzer, the sampledilution device for supplying a diluted sample to the analyzer forspectrometry analysis thereof, the diluted sample comprising one or moretrace elements and matrix, wherein: a) the device comprises a firststructure configured to dilute a first portion of a sample by a dilutionfactor; b) the analyzer is configured to receive and analyze the dilutedportion of the sample and determine a matrix level in the dilutedportion of the sample; and c) the device further comprises a devicecontroller comprising data related to a predetermined matrix level, thedevice controller configured to receive data from the analyzer which isrelated to the determined matrix level in the diluted portion of thesample and configured to control the dilution of the remainder of thesample based on a comparison between the determined matrix level and thepre-determined matrix level by adjusting the dilution factor based onthe comparison between the determined matrix level and thepre-determined matrix level.
 15. The device of claim 14, wherein thedevice controller is arranged to compare the determined matrix levelwith a pre-determined maximum matrix level and to adjust the dilutionfactor for the sample based on the comparison.
 16. The device of claim15, wherein the device controller is arranged to increase the dilutionfactor if the determined matrix level is above the pre-determinedmaximum matrix level.
 17. The device of claim 15, wherein thepre-determined maximum matrix level is 2000 mg/I.
 18. The device ofclaim 15, wherein the device controller is arranged to decrease thedilution factor if the determined matrix level is below thepre-determined maximum matrix level.
 19. The device of claim 14, whereinthe device controller is arranged to dilute the sample by a firstdilution factor and to adjust the first dilution factor to a seconddilution factor based on the determined matrix level.
 20. The device ofclaim 19, wherein the first dilution factor is
 100. 21. The device ofclaim 19, wherein the device controller is arranged to calculate thesecond dilution factor by comparing the determined matrix level with apre-determined maximum matrix level.
 22. The device of claim 14, whereinthe device controller is arranged to adjust a flow rate of a diluentrelative to a flow rate of the sample upstream of a mixing region forproviding the diluted sample.
 23. The device of claim 14, furthercomprising a mass spectrometer for mass analyzing the diluted sample toprovide the data comprising the determined matrix level to the devicecontroller.
 24. The device of claim 23, wherein the mass spectrometercomprises an inductively coupled plasma mass spectrometer.
 25. Thedevice of claim 14, wherein the device controller is arranged to controlthe dilution of the sample in real time as the matrix level isdetermined from the received data from the analyzer.
 26. Anon-transitory computer-readable medium on which is stored a computerprogram comprising instructions which, when run on a computer, cause thecomputer to carry out the method of claim 1.